Culture

AUSTIN, TEXAS (March 25, 2019)--Training interventional radiologists to perform endovascular thrombectomies results in positive outcomes for patients experiencing stroke, according to a study presented today at the Society of Interventional Radiology Annual Scientific Meeting. Expanding access to this treatment provides patients timely access to this gold-standard treatment.

"With a limited availability of providers, thrombectomy is only available to 2 to 3 percent of eligible patients in the United States," said Kelvin Hong, MD, FSIR, associate professor and division chief of interventional radiology at Johns Hopkins University. "Patients don't plan where and when they have a stroke. Our model of training board-certified interventional radiologists can expand access to quality, evidence-based care, and reduce the lifelong disability associated with stroke."

Thrombectomy, a treatment that clears a clogged artery in the brain, increases the survival rates among those suffering an acute ischemic stroke, reduces the likelihood of resulting disabilities, and speeds function recovery. However, to gain these benefits, thrombectomies must be initiated and performed quickly. Many hospitals do not have providers available to perform these treatments and must transfer patients to a facility where they can get this care, losing valuable time.

To determine an efficient and sustainable way to expand access to thrombectomy, researchers from Johns Hopkins University developed an interventional radiology stroke team at Suburban Hospital, a community hospital in Montgomery County, Maryland, a suburb of Washington, D.C. The team consisted of four interventional radiologists who were specially trained by a neurointerventional radiologist for six months. The entire team was available 24 hours a day, seven days a week with the neurointerventional radiologist helicoptered to the hospital for every case during this training period.

"We looked to change the dynamic in stroke care, where instead of transporting medically fragile patients, we brought in a specialist to perform this care and build the infrastructure necessary to provide this treatment to a community with limited stroke care resources," said Ferdinand Hui, MD, a neurointerventional radiologist and associate professor of radiology and radiological science at Johns Hopkins University. "In a situation where every minute counts, we wanted to design our program to provide the training and organization necessary to bring 24/7 highly trained stroke interventionalists online as quickly as possible."

Once the interventional radiologists were conducting the treatments independently, researchers measured the technical success of the thrombectomies performed by the newly trained physicians in 35 stroke cases using the Thrombolysis in Cerebral Infarction (TICI) scale and found no significant differences compared to the 2016 HERMES meta-analysis of endovascular thrombectomy outcomes performed by other practitioners, such as neurointerventional radiologists and neurosurgeons. Additionally, 14 percent mortality in the first 90 days after the procedure was similar to 15.3 percent 90-day mortality among patients at stroke centers evaluated through the Journal of the American Medical Association-published HERMES trial. The median interval from symptom onset to the point when blood flow was restored was 325 minutes, compared to 285 minutes in previous research.

Researchers plan to further evaluate the technical outcomes and time metrics in a second-year study with a goal of further reducing the time to treat each patient by improving efficiency and optimization year over year.

A limitation of the study may be in whether hospitals of varying sizes and resources can reproduce the program with the same outcomes. The research team plans to re-evaluate the program after two years of data collection.

Police use of body-worn cameras is growing rapidly in the United States. New research that looked at 70 studies of body-worn cameras concludes that while officers and citizens generally support using the cameras, the devices may not have had significant or consistent effects on most measures of behavior by officers or citizens, or on citizens' views of the police.

The study, by researchers at George Mason University's (GMU) Center for Evidence-Based Crime Policy, appears in Criminology & Public Policy, a publication of the American Society of Criminology.

"Expectations and concerns surrounding body-worn cameras among police leaders and citizens have not yet been realized by and large in the ways anticipated by each," according to Cynthia Lum, professor of criminology, law, and society at GMU, who led the study. "It's likely that body-worn cameras alone will not be an easy panacea for improving police performance, accountability, and relationships with citizens."

Researchers examined 70 empirical studies of body-worn cameras published in the United States and globally through June 2018. The studies addressed the impact of body-worn cameras on officers' behavior and on officers' attitudes toward body-worn cameras, as well as the impact of the devices on citizens' behavior, and citizens' and communities' attitudes toward body-worn cameras. The studies also considered the impact of body-worn cameras on criminal investigations and on law enforcement organizations.

The researchers found that in general, officers seem supportive of body-worn cameras, especially as they gain more experience with them. However, the devices have not produced dramatic changes in police behavior, the study concludes. Other findings from the study:

Body-worn cameras seem to reduce complaints against officers, but it is unclear whether and to what degree these changes reflect citizens' reporting behaviors or improvements in officers' behavior or their interactions with citizens. It is also unclear if the devices improve citizens' satisfaction with police encounters, as might be expected if the cameras affected police behavior substantially.

Wearing body-worn cameras has not led to de-policing, also known as a "Ferguson effect" in which officers pull back from being productive in their duties. Cameras do not seem to discourage police contacts or officer-initiated activities, and arrests seem as likely to increase or decrease with use of the devices.

Citizens are also generally supportive of police using body-worn cameras, but it's unclear that their use improves citizens' views of police, their behaviors toward police officers, or their relationships with police.

"To maximize the positive impacts of body-worn cameras, we suggest more attention to the ways and contexts--organizational and community--in which the devices are most beneficial or harmful," notes Christopher S. Koper, associate professor of criminology, law, and society at GMU, who coauthored the study. "Attention should also be paid to how the cameras can be used in police training, management, and internal investigations to improve police performance, accountability, and legitimacy in the community."

When the Human Genome Project was completed, in 2003, it opened the door to a radical new idea of health - that of personalized medicine, in which disease risk and appropriate treatment would be gleaned from one's genetic makeup. As more people had their genomes sequenced, disease-related genes would start coming into view-- and while this is true in many ways, things also turned out to be much more complicated.

Sixteen years on, tens of thousands of people have had their genomes sequenced yet it remains a major challenge to infer future health from genome information. Part of the reason may be that genes interact with each other to modify trait inheritance in ways that aren't totally clear, write Donnelly Centre researchers in an invited perspective for the leading biomedical journal Cell.

"All the genome sequencing data is highlighting the complexity of inheritance for the human genetics community," says Brenda Andrews, University Professor and Director of U of T's Donnelly Centre for Cellular and Biomolecular Research and a senior co-author, whose lab studies interactions between genes. "The simple idea of a single gene leading to a single disease is more likely to be an exception than a rule," she says.

Andrews and Charles Boone, who is also a senior co-author, are professors in U of T's Donnelly Centre and the Department of Molecular Genetics, as well as Senior Fellows of the Genetic Networks program at the Canadian Institute for Advanced Research, which Boone co-directs.

Genome wide association studies, or GWAS, which scan the genomes of patient populations and compare them to healthy controls, have unearthed thousands of mutations, or genetic variants, that are more prevalent in disease. Most variants are found in common diseases that affect large swathes of the world's population but their effects can be small and hard to see. Instead of there being a single gene for heart disease or schizophrenia, for example, there may be many combinations of subtle genetic changes scattered across the genome that tune up or down a person's susceptibility to these diseases.

Vast genetic diversity in the human population further influences trait inheritance while environmental effects, such as diet and upbringing, further complicate matters.

In some cases, a single gene variant can be extremely potent and cause a disease, as seen in cystic fibrosis, heamophilia and other inherited disorders. But even two people with the same disease variant can experience a wildly different disease severity which, presently, cannot be gleaned from their genomes. Even more astonishing, sequencing studies have identified people who carry damaging mutations but remain perfectly healthy, presumably protected by other, as yet unknown gene variants within their genomes.

"It would be a simpler problem if one particular mutation resulted in Disease X all of the time, but that's often not the case," says Michael Costanzo, Senior Research Associate in Boone's lab and one of the authors on the paper. "To understand the effect of combinations of variants is really difficult. We suspect it's particular sets of mutations that really impact what the disease outcome is going to be in a personal genome" says Costanzo. "How genes interact with each other is important and, given our current understanding of gene-gene interactions, it's not a problem that's easily solved by reading individual genome sequences."

It's a numbers game as most genome analysis methods lack the statistical power to confidently uncover multiple genes behind a disease. An often-cited calculation, by researchers at the Broad Institute in Boston, states that to identify a single pair of genes underlying a disease, on the order of half a million patients would have to have their genomes sequenced, with another half a million of healthy people as controls. "If most genetic diseases involve gene combinations, collecting enough patient data to find these interactions is a huge challenge," says Costanzo.

Genetic interactions - what are they and how can they be identified?

"The concept of genetic interaction is simple, but the physiological repercussions can be profound," write the authors. Two genes are said to interact if a combined outcome of their defects is bigger or lesser than expected from their individual outcomes. For example, a person carrying a mutation in either gene A or in gene B can be healthy, but if both A and B don't work, disease occurs.

Research in simple model organisms--most notably yeast--has mapped genome-wide genetic interactions revealing how thousands of genes organize into functional groups within a network. From this, basic principles emerged, allowing researchers to predict a gene's function and its relative importance for the cell's health based on its position in the network. Studies also revealed the identity of so-called "modifier genes" which can suppress the effect of damaging mutations and how genetic background influences trait inheritance.

These types of studies rest on the researchers' ability to switch off genes in precise combinations to find the ones that work together. For human genes, however, such tools did not exist until very recently.

That's all changed now thanks to the gene editing tool CRISPR with which human genes can be turned off in any combination with ease. Although no genome-wide map is yet available, early work indicates that the same principles uncovered in model organisms also apply to human genes. This is already helping reveal function of the less studied human genes and how they relate to disease. And with new computational approaches, it is becoming possible to integrate findings from model organisms with incoming human data to achieve an emerging glimpse of more meaningful insights about health from genome information.

Genetic interactions and cancer therapy

Freed from normal checks and balances, cancer cells stockpile mutations in their genomes and this sets them apart from healthy cells in a way that can be exploited for therapy. Knowing how genes interact in cancer holds promise for the development of selective drugs that kill only sick cells and leave healthy ones unharmed.

"Cancer is a genetic disease and ultimately the genetic wiring of a cancer cell is a product of mutations that occur its genome and we want to understand that," says Jason Moffat, a co-author on the paper and a professor of molecular genetics in the Donnelly Centre whose lab uses CRISPR to map genetic interactions in cancer cells. "With CRISPR, we can start to systematically map how genes interact in cancer cell lines in a similar fashion to how geneticists have mapped genetic interactions in yeast," he says.

This work has the potential to reveal distinct drug targets for different forms of disease. The goal is to find a drug that synergizes with a mutation that's only found in a type of cancer. The drug would then kill sick cells more precisely and with fewer side effects than chemotherapy or radiotherapy.

The knowledge of genetic interactions will also help shed light on why so many approved cancer drugs only work in some patients and not others.

"We can't think about genes in isolation anymore," says Boone. "We have to start looking at variants of multiple genes as a major component of genetic disease, because those combinations are going to be different for different people and these specific combinations may not only profoundly affect disease susceptibility, but they will likely dictate new personalized therapies."

Indigenous peoples in Canada have high rates of psychological distress, suicidal thoughts and suicide attempts, and these mental health issues are linked to income inequalities, found a study published in CMAJ (Canadian Medical Association Journal).

Suicide is a major cause of death among First Nations, Métis and Inuit people, with rates 2 to 3 times higher than in non-Indigenous Canadians.

"We found persistent and substantial income-related inequalities in psychological distress and suicidal behaviours among Indigenous peoples living off-reserve in Canada, including status First Nations, non-status First Nations, Métis and Inuit," says Dr. Mohammad Hajizadeh, School of Health Administration, Dalhousie University, Halifax, Nova Scotia.

Of the 14 410 adults included in the study representing more than 600 000 Indigenous people in 2012, the rate of lifetime suicidal ideation (thoughts of suicide during their life), was 16% for men and 22% for women, with rates for lifetime suicide attempts at 2% for men and 2.3% for women. Using a scale to measure psychological distress, the researchers found the score for men was 15.2 and 16.7 for women (with 10 indicating no distress and 50 indicating severe distress.)

Data came from the Aboriginal Peoples Survey conducted by Statistics Canada.

Poorer individuals disproportionately experienced higher psychological distress, suicidal ideation and suicide attempts. Food insecurity -- the uncertainty over having a regular, affordable source of nutritious food -- appeared to be a key factor explaining the higher rates of mental health issues among low-income Indigenous peoples. The authors suggest focusing on improving the social determinants of health, such as income, employment and food availability, to address mental health among poor Indigenous people.

"Policies designed to address food insecurity and income may help improve mental health outcomes among low-income Indigenous peoples living off-reserve," says Dr. Hajizadeh.

"Socioeconomic inequalities in psychological distress and suicidal behaviours among Indigenous peoples living off-reserve in Canada" is published March 25, 2019.

Tokyo, Japan - Researchers from Tokyo Metropolitan University have shown that the tunable hydrophobic nature of dense siloxane gels is strongly correlated with their catalytic activity, explicitly demonstrating how molecules with different hydrophobic nature at the molecular level interact differently with surfaces of differing hydrophobicity. This is also the first time a siloxane gel has been shown to be highly effective for the reaction of silyl ethers, commonly used as a protecting agent.

The word hydrophobic comes from ancient Greek, "hydro" for water and "phobia" for fearing (opposite of hydrophilic). Thus, a hydrophobic material is one which repels water; household examples include coatings for non-stick frying pans and smartphones. Hydrophobicity also plays a key role in nature, for example, how certain plants and animals harvest water from the atmosphere, and how long strands of DNA are efficiently packed into chromosomes. In recent years, it has also been revealed to be part of the function of acid catalysts, acidic materials which can speed up chemical reactions, widely used in the petrochemical industry. Though it was widely known that more hydrophobicity led to better catalysis, it was not clear why this was the case, due to the heterogeneous porous structure of the most common catalysts.

Thus, a group of researchers led by Dr Hiroki Miura and Prof Tetsuya Shishido from Tokyo Metropolitan University studied the catalytic activity of a dense siloxane gel, a kind of silicone rubber, with acidic sulfo groups attached. Importantly, these gels can be covered with controlled amounts of both acid groups and hydrophobic methyl groups, enabling fine control of hydrophobicity. These gels are also not porous, presenting a surface which is covered in only two key groups, allowing for simpler but more accurate quantitation of surface environment. The group studied catalysis of the hydrolysis (bond breakage with water) of alkyl acetates, commonly used for producing paints, fragrances, and even plastics; they found that acetates with longer, more hydrophobic tails in their molecular structure benefited from increased catalysis with a lower sulfo-to-methyl ratio. On the contrary, less hydrophobic molecules were catalysed less effectively due to less available sulfo groups. They clearly demonstrate how the affinity of water to catalysis sites can hinder the approach of different molecules; this may be leveraged to engineer both selectivity and increased activity.

Furthermore, the siloxane catalyst was applied to the deprotection of silyl ethers. Silyl ethers are protecting groups, attached to groups which need shielding from unwanted reactions. In order to make them available again, they must be readily deprotected. The group showed, for the first time, that siloxane gel catalysts are highly effective in deprotecting silyl ethers, a key reaction step in common reactions such as the construction of artificial nucleotides (or DNA). With more understanding of how molecular environment is tied to function, they hope that further chemical enhancements to these catalysts may open the way to new functions and applications.

NEW ORLEANS--When trying to lose weight by cutting calories, people who have obstructive sleep apnea (OSA) in addition to obesity can lose more weight if they treat their sleep disorder with an overnight CPAP, or continuous positive airway pressure, machine. This finding of a new study will be presented Saturday at ENDO 2019, the Endocrine Society's annual meeting in New Orleans, La.

"Some people may think if they lost weight, they may not need the CPAP machine," said lead investigator Yuanjie Mao, M.D., Ph.D., an endocrinology fellow physician at the University of Arkansas for Medical Sciences (UAMS), in Little Rock, Ark. "However, our study finds the opposite for people with obesity and OSA who try to lose weight by restricting calories: CPAP treatment can actually result in more weight loss."

OSA, most often caused by obesity in adults, is a common sleep disturbance in which breathing repeatedly stops and starts during sleep. Wearing a CPAP mask during sleep is the first-line treatment of OSA and is widely recommended with weight loss for patients with obesity, despite a lack of scientific evidence to support this strategy, Mao said.

To test the effect of CPAP therapy on weight loss, Mao and his co-workers evaluated the medical records of 501 adults, all with obesity, treated in a UAMS weight loss clinic from January 2014 through August 2017. All patients underwent an intensive 16-week program that included eating a very-low-calorie diet of 800 calories a day, as well as exercise programs, weekly individual counseling and cognitive behavioral therapy. Of the 300 patients eligible for the study, the researchers divided them into three groups based on their self-reported OSA symptoms.

A total of 89 patients reported no symptoms of OSA and therefore had no OSA treatment. Another 164 patients had OSA symptoms but did not receive a CPAP machine, whereas 47 patients had OSA symptoms and received treatment with a CPAP machine. Because not all the patients had a sleep study, the researchers could not determine their OSA severity, said senior investigator Peter Goulden, M.D., F.R.C.P., an endocrinologist at UAMS.

Among patients with self-reported OSA symptoms, those who received concurrent CPAP treatment lost an average of 5.7 pounds more in four months than patients who did not treat their sleep apnea, Mao reported. In total, the CPAP-treated group lost more than 26.7 pounds on average versus almost 21 pounds for patients who did not treat their OSA symptoms using CPAP. The group without OSA symptoms lost approximately 19 pounds over 16 weeks.

When the researchers adjusted their statistical analyses for patients' beginning weight, age and sex, they still found a correlation between CPAP treatment and absolute weight loss, Mao said.

He suggested that sleep quality and underlying neuroendocrine changes might explain their results. CPAP treatment can enhance sleep quality, and some research shows that good sleep quality may improve weight control.

NEW ORLEANS--Caucasians and Hispanics with diabetes have a greater risk of fracture compared to those without diabetes, while African Americans with diabetes have little to no additional fracture risk, according to a study to be presented Saturday, March 23 at ENDO 2019, the Endocrine Society's annual meeting in New Orleans, La.

"Diabetes has been associated with additional risk of fracture, but it had not been well studied in African Americans or Hispanics, the two racial-ethnic groups with the highest rates of diabetes in the United States," said lead researcher Rajesh Jain, M.D., of the Lewis Katz School of Medicine at Temple University in Philadelphia, Pa.

He noted that because of the additional fracture risk associated with diabetes, some medical groups have suggested additional osteoporosis screening or treatment to help prevent fractures in patients with diabetes. "This research could mean that African Americans with diabetes may not require the additional screening or treatment for osteoporosis that Caucasians or Hispanics with diabetes may require," Jain said.

The researchers evaluated data from 19,153 people with diabetes (7,618 Caucasian, 7,456 African American and 4,079 Hispanic) and 26,217 people with hypertension (15,138 Caucasian, 8,301 African American, and 2,778 Hispanic), all at least 40 years of age.

When controlling for other important factors, the risk of fracture in white and Hispanic people with diabetes was 23 percent higher than those without diabetes. However, the risk of fracture in African Americans with diabetes was not significantly different than those without diabetes.

"This is a novel finding and has not been previously reported," Jain said.

African Americans, regardless of whether they had diabetes, had more than 10-fold risk of a fracture if they had a fracture in the past, compared with about a two-fold increased risk in white and Hispanic people.

"This suggests risk factors for fracture may differ in African Americans," Jain said.

Treating women with thyroid antibodies but a normal thyroid function with a medicine called Levothyroxine does not make them more likely to deliver a live baby, new research led by the University of Birmingham suggests.

The research, which was led by researchers from the Institute of Metabolism and Systems Research, Birmingham Clinical Trials Unit, the Institute of Applied Health Research, and Tommy's Centre for Miscarriage Research at the University of Birmingham, was published today (March 23rd) in New England Journal of Medicine. Funded by the MRC and the National Institute for Health Research (NIHR), the research was also presented today at ENDO 2019, the Endocrine Society's annual meeting in New Orleans, USA.

Miscarriage occurs in one in five women who conceive, making it one of the most common complications of pregnancy. Previous research has found a strong association between the presence of thyroid peroxidase antibodies and miscarriage. However, it was unclear from previous evidence whether treating women with normal thyroid function and with thyroid peroxidase antibodies with Levothyroxine would improve live-birth rates.

The University of Birmingham has now led the largest study of its kind to investigate whether treatment with Levothyroxine would increase the rates of live births at or beyond 34 weeks gestation among women who have thyroid antibodies and also a history of miscarriage or reduced fertility.

Lead author Dr Rima Dhillon-Smith, an academic clinical lecturer at the University of Birmingham, said: "Our research has found that Levothyroxine treatment, started before pregnancy, in women with normal thyroid function and thyroid peroxidase antibodies who have a history of miscarriage or infertility, does not improve the chances of live birth.

"We were surprised by the results of our study as previous small studies suggested there could be a benefit of Levothyroxine treatment in women with thyroid antibodies."

The authors conducted a study of 940 women at 49 UK hospitals with normal thyroid function aged between 16 and 41 who were positive for thyroid peroxidase antibodies; had a history of miscarriage or infertility, and were trying to conceive naturally or with assisted conception.

The study, carried out between 2011 and 2017, saw 470 women receive 50mcg daily of Levothyroxine and 470 women receive a daily placebo. The participants began taking the medication before they conceived and continued until the end of their pregnancy.

Outcomes in both groups were similar: 266 of the 470 (56.6 per cent) women who received Levothyroxine, and 274 of 470 (58.3 per cent) women who received a placebo, became pregnant; 176 women (37.4 per cent) taking Levothyroxine, and 178 (37.9 per cent) taking a placebo, had live births.

Dr Rima Dhillon-Smith added: "Thyroid peroxidase antibodies are found in the blood in approximately one in 10 women who have normal thyroid function, and they have been linked to increased risk of miscarriage and preterm birth.

"International guidelines currently recommend the consideration of Levothyroxine treatment for women with thyroid antibodies, as there is thought to be minimal chance of harm and a potential to help increase the chance of having a live birth.

"As our study was large and of high quality, we can now be confident that Levothyroxine does not improve pregnancy success for women with thyroid antibodies and normal thyroid function and therefore should not be recommended or used in clinical practice. This will mean no longer providing unnecessary medication to women who do not need it."

Dr Kristien Boelaert, also of the University of Birmingham, said: "Our trial has definitively answered an important clinical question.

"In a recent survey we carried out of UK fertility clinicians almost 40 per cent said they routinely use Levothyroxine in women with thyroid peroxidase antibodies to reduce miscarriage and pre-term birth.

"We now pose the question of whether testing for thyroid peroxidase antibodies should be performed at all in women with infertility or previous miscarriages.

"While thyroid peroxidase antibodies testing may inform about future risk of progression to thyroid disease, our research has shown its treatment with Levothyroxine does not improve pregnancy outcomes and may only generate patient anxiety and unnecessary healthcare costs.

"We hope that national and international guidelines are updated to remove current recommendations which advise consideration of the use of Levothyroxine in these women.

"We also hope that the current practice of routine testing of thyroid peroxidase antibodies in high risk populations such as women with miscarriage and reduced fertility is re-considered."

Tokyo, Japan - Researchers from Tokyo Metropolitan University have shown that a newly engineered catalyst made of gold nanoparticles supported on a metal oxide framework shows breakdown of ammonia impurities in air, with excellent selectivity for conversion to nitrogen gas. Importantly, it is effective at room temperature, making it suitable for everyday air purification systems. The team successfully identified the mechanism behind this behavior, paving the way towards the design of other novel catalytic materials.

The distinctive, sharp odor of ammonia is familiar to many. It is a common industrial chemical, primarily used as feedstock for fertilizers as well as disinfectants in both household and medical settings. It is also highly toxic when concentrated; the United States Occupational Safety and Hazard Administration has a strict upper limit of 50 parts per million in breathing air averaged over an eight-hour working day and forty-hour working week. Given its wide industrial use and presence in nature, it is paramount that effective measures be in place to remove unwanted ammonia from the atmosphere in our everyday working and living environments.

Catalysts, like the ones found in the catalytic converters of cars, can help solve this problem. Unlike filters which simply trap harmful substances, catalytic filters can help break ammonia down into harmless products like nitrogen gas and water. Not only is it safer, preventing the buildup of toxic chemicals, it also makes it unnecessary to replace them regularly. However, common existing catalysts for ammonia only function at temperatures of over 200 degrees Celsius, making them inefficient as well as inapplicable for household settings.

Now, a team led by Project Professor Toru Murayama from Tokyo Metropolitan University has designed a catalytic filter which can function at room temperature. Consisting of gold nanoparticles stuck onto a framework of niobium oxide, the newly designed filter is highly selective in what it converts ammonia to, with nearly all conversion to harmless nitrogen gas and water and no nitrogen oxide byproducts. This is known as selective catalytic oxidation (SCO). They collaborated with industrial partners from NBC Meshtec Inc. to produce a working prototype; the filter has already been applied to reduce gases contaminated with ammonia to undetectable levels.

Importantly, the team also successfully uncovered the mechanism by which the material works. They showed that gold nanoparticles play an important role, with increased loading leading to increased catalytic activity; they also found that the choice of framework was extremely important, showing experimentally that chemical sites known as Brønsted acid sites on the niobium oxide backbone played an important role in how selective the material was. The team hopes that general design principles like this may find application to the creation and modification of other catalytic materials, extending their growing range of applications.

Current approaches to identifying people who are at high risk for overdosing on opioids target many who are not truly at high risk. A new study sought to develop and validate a way to predict the risk of opioid overdose among Medicare beneficiaries with at least one opioid prescription. The model the researchers developed was more effective in predicting risk of overdose than traditional statistical models.

The study, by researchers at the University of Florida, University of Pittsburgh, Carnegie Mellon University, and the University of Utah, appears in JAMA Network Open.

"Our model was effective in dividing the participants into three risk groups according to predicted risk score, with three-quarters in a low-risk group with a negligible rate of overdose, and more than 90 percent of individuals with overdose captured in the high- and medium-risk groups," explains Jeremy C. Weiss, assistant professor of health informatics at Carnegie Mellon University's Heinz College, who participated in the study.

"The ability to identify such risk groups has important implications for policymakers and insurers who currently target interventions based on less accurate measures to identify patients at high risk," according to Wei-Hsuan "Jenny" Lo-Ciganic, assistant professor of pharmaceutical outcomes and policy at the University of Florida, who was lead author on the study.

In 2017-2018, researchers studied 560,057 fee-for-service Medicare beneficiaries without cancer who filled one or more prescriptions for opioids between 2011 and 2015. Those individuals were randomly assigned and equally divided into subgroups. Every three months, the researchers measured potential predictors of opioid overdose, including participants' socio-demographic characteristics (e.g., age, sex, disability status), health status, patterns of opioid use, and factors related to the participants' practitioners and the regions where they lived. The researchers then identified opioid overdoses from inpatient and emergency room claims, and predicted risk of overdose in the three months after participants began treatment with the drugs.

The study found that the machine-learning algorithms the researchers developed performed well in predicting risk of opioid overdose and identifying subgroups of patients at similar risk of overdosing, especially when it came to identifying individuals with a low risk of overdosing. Machine learning is an alternative analytic approach to handling complex interactions in large data, discovering hidden patterns, and generating predictions in clinical settings. Based on their findings, the researchers concluded that their approach outperformed other methods for identifying risk, such as traditional statistical models.

The authors caution that their study looked only at patients who obtained opioids from medical settings, not those who got them from nonmedical settings, which are not captured in claims data. In addition, the study looked at overdoses in medical settings, not overdoses outside those settings.

"Machine-learning models that use administrative data appear to be a valuable and feasible tool for identifying more accurately and efficiently individuals at high risk of opioid overdose," says Walid Gellad, associate professor of medicine at the University of Pittsburgh and senior author on the study. "Although they are not perfect, these models allow interventions to be targeted to the small number of individuals who are at much greater risk."

Did you know that music and diagnostic imaging have something in common? Sounds have a lower or higher pitch depending on the size of the object that creates them. Tubas and double basses are big and produce deep low-pitch sounds, while flutes and violins are small and produce high-pitched sounds. What's interesting is that the same effect occurs when biological structures like cells or tissues emit sound - the pitch varies with size.

But what kind of sounds do biological structures make? Moreover, how can we listen to them?

Capitalizing on the correlation between size and pitch, a Ryerson-led research team working out of the Institute for Biomedical Engineering, Science & Technology (iBEST) at St. Michael's Hospital recently developed a mode of imaging so novel that their study results were published in the Nature journal, Communication Physics.

An appreciation of this breakthrough begins with the basics of Photoacoustic (PA) imaging, a modality that is quickly gaining traction in biomedical research. Like its cousin Ultrasound (US) imaging, PA imaging creates a visual image of biological structures by collecting sound waves.

While US imaging technology involves sending soundwaves into a biological structure and listening to the echoes as they bounce around, PA imaging technology does something entirely different.

"With photoacoustic imaging, we project light into structures that will absorb it, such as blood vessels," says Dr. Michael Kolios, the PA imaging pioneer who supervised the study. "Light waves cause biological structures to heat up by a tiny fraction, which triggers an almost imperceptible expansion in volume. When that happens, sound is generated, like thunder after a lightning strike."

Most existing PA imaging techniques measure amplitude (loudness), displaying areas emitting louder sounds with brighter pixels. What the Ryerson-led team set out to develop was a technique that would measure the frequency (pitch) of sounds emitted from biological structures.

"Depending on the size of a biological structure, the pitch of the sound waves it emits will be higher or lower," says Dr. Michael Moore, a Medical Physics Resident at Grand River Hospital in Kitchener who led the research team as a doctoral student under the supervision of Kolios. "If we could filter incoming sounds by frequency, we could create images that focus on structures of a particular size, which would help to reveal features that might otherwise be hidden or less prominent."

The team developed a technique they call F-Mode (for frequency), which enabled them to subdivide PA signals into different frequency bands. They then successfully demonstrated selective enhancement of features of different sizes in samples ranging from biological cells to live zebrafish larvae - all without the use of contrast dyes that would typically be required by other state-of-the-art imaging techniques.

Moore and Kolios are quick to point out that a key to their success was the opportunity to work at iBEST and with Dr. Xiao-Yan Wen and his team at Zebrafish Centre for Advanced Drug Discovery. "Without the knowledge and expertise of the team at the Wen Lab, it would not have been possible to demonstrate that our technique works," says Moore.

The research team, which includes Ryerson Biomedical Physics doctoral candidates Eno Hysi and Muhannad Fadhel, is now taking steps toward translating F-Mode into clinical applications, where it will be of widespread benefit. For example, the ability to segment and enhance features of different scales has significant potential in areas such as ophthalmology, neurosurgery and the detection of various conditions such as hypertension.

INDIANAPOLIS - While the importance of trusted relationships between patients and their physicians is taken for granted, little attention has been given to the relationships among physicians themselves. Yet the interactions between, for example, a patient's primary care physician and cardiologist or between a patient's pediatrician and an oncology team, are essential to the safety and quality of care for patients and the resilience of physicians and other healthcare professionals.

In a Viewpoint article,” Physicians’ Trust in One Another,” published online March 22 and in the April 9 print edition of JAMA, authors Richard M. Frankel, Ph.D. of the Regenstrief Institute; Virginia P. Tilden, Ph.D. of Oregon Health & Science University and Anthony Suchman, M.D. of the University of Rochester write that while trust in the physician to physician relationship hasn’t been closely examined, it appears increasingly to be at risk.

"If doctors don't value and trust one another, the safety and quality of patient care is potentially at risk of being compromised," said Dr. Frankel, a health services researcher and medical sociologist, who is first author of the article. "Trust is important for any well-functioning system, and we know that for the healthcare system to work successfully, trust has to be invested at every level in that system."

Where does this apparent lack of trust originate? Dr. Frankel looks back to the competitiveness of medical school and as medical school ends, the competition for residencies. Do those who enter the most selective (and in the United States, the most highly paid) specialties look down on their primary care colleagues? Do specialists have a lack of trust in their primary care peers' judgements simply because they chose a less specialized medical career like pediatrics or family practice?

Noting that the use of electronic medical records and the development of specialties such as hospital medicine have removed much of the interpersonal interaction that used to take place between primary care physicians and specialists -- the phone call to discuss a case or the hallway update -- Dr. Frankel voices concern that, in addition to having a potentially negative impact on patient care, the lack of interpersonal interaction may also be contributing to the increase in physician burnout and decreased resilience.

"Diversity of opinions, a critical eye and skepticism are all healthy and enable you to provide good care as well as to uncover errors when they do occur," Dr. Frankel said. "But if a physician does not have confidence in colleagues and, instead, develops attitudes that are inherently cynical and distrustful of others, you have a system that is at risk to do harm to patients, and equally importantly, those who provide care on a day to day basis."

The JAMA authors highlight three initial principles to bolster physician to physician relationships:

Recognize that physician-physician relationships are consequential and should be given the same level of attention and intention as patient-physician and interpersonal (doctor-nurse, for example) relationships

Value differences in perspective; harness them as a resource

Notice the quality of relationships in each moment; be accountable for creating patterns of respect and hold others accountable for creating patterns of respect and collaboration

"We need a lot more focus on physicians' trust in one another to both (1) better understand how the medical system is succeeding or failing us -- and I believe at present it is failing -- and (2) to help devise a prescription for building, and in some cases re-building physician to physician trust," Dr. Frankel said. "Given the climbing rates of medical errors in the United States, physicians clearly need better ways of relating to each other and working together."

He believes that the problem needs to be addressed across the spectrum from medical school students to practicing primary care and specialist physicians.

LA JOLLA--(March 22, 2019) Similar to the dozens of Sherpas that guide hikers up treacherous Himalayan mountains to reach a summit, the nervous system relies on elaborate timing and location of guidance cues for neuronal axons--threadlike projections--to successfully reach their destinations in the body. Now, Salk Institute researchers discover how neurons navigate a tricky cellular environment by listening for directions, while simultaneously filtering out inappropriate instructions to avoid getting lost. The findings appeared in Neuron on March 19, 2019.

"There are 100 trillion connections in the nervous system governed by 20,000 genes, of which roughly 10 gene families are known to be involved in controlling axon guidance. We wanted to understand the clever genetic systems nature has employed to wire the most complicated biological machine in the universe," says Salk Professor Samuel Pfaff, senior author and a Howard Hughes Medical Institute investigator. "Thus, we set out to examine how motor neurons find their connections with muscles in the body, which is critical for our brain to relay information to our muscles to allow for movement."

The brain controls hundreds of different muscles to allow for precise movement. During development, motor neurons in the spinal cord extend their axons outside of the central nervous system to connect with muscle cells in the body. Every motor neuron relies on a set of genes to ensure the axon grows correctly to the muscle.

"In the broadest sense, we hoped that by identifying genes involved in abnormal motor neuron development we could better understand the intricacies of cell signaling in other contexts such as cancer," says first author Dario Bonanomi, a former postdoctoral fellow in the Pfaff lab, now a group leader at the San Raffaele Scientific Institute. "This work not only shows us how the nervous system develops, but also how cells, more generally, communicate, move and create structures in the body."

To find genes important for motor-neuron axon guidance, the team carried out a genetic screen and observed where the motor neurons grew their axons using green fluorescent proteins in a mouse model they engineered. The team then traced the axons to see when correct and incorrect growth decisions were made. Through this axon tracing, the scientists identified a gene mutation that caused motor axon misrouting. In this case, the motor neuron axons took detours and never connected properly to the muscles.

Upon closer investigation, the scientists found that these motor neurons climbed up the edge of the spinal cord rather than properly exiting to meet their muscle targets. The team pinpointed the gene causing this detrimental mutation as p190, which was previously known to play a role in cancer suppression, but had not been implicated in establishing neuronal connections during development.

The researchers set up a series of experiments to examine how p190 affects axons leaving the spinal cord. They found that, although axons are normally attracted to a protein in the spinal cord called netrin, during a short time window p190 acts as a blinder, so the axons disregard netrin and are led outside of the spinal cord. After the axons safely leave the central nervous system, this blinder is removed. Without p190, the axons are attracted to netrin and do not properly leave the spinal cord, so never connect with muscles.

Pfaff, holder of the Benjamin H. Lewis Chair, adds, "These results provide mechanistic insight into the unimagined complexity that cells use to communicate with one another."

The next step is to examine the control mechanism of p190, and what factors impact the timing of its activity, say the researchers.

CHAMPAIGN, Ill. -- A new study in mice suggests that consuming the chemical compounds found in thermally abused cooking oil may trigger genetic changes that promote the progression of late-stage breast cancer.

Thermally abused frying oil - cooking oil that has been repeatedly reheated to high temperatures - may act as a toxicological trigger that promotes tumor cell proliferation, metastases and changes in lipid metabolism, scientists at the University of Illinois found. They reported their findings in the journal Cancer Prevention Research.

After consuming a low-fat diet for one week, one group of the mice was fed unheated fresh soybean oil, while another group consumed thermally abused oil for the next 16 weeks. Soybean oil was used in the study because of its common use by the food service industry in deep frying.

The U. of I. scientists simulated late-stage breast cancer by injecting 4T1 breast cancer cells into a tibia of each mouse. The 4T1 cells are an aggressive form of the disease that can spontaneously metastasize to multiple distant sites in the body, including the lungs, liver and lymph nodes, according to the study.

Twenty days after inoculation with the tumor cells, the primary tumors in the tibias of the mice that consumed the thermally abused oil had more than four times as much metastatic growth as the mice that consumed the fresh soybean oil. And when the researchers examined the animals' lungs, they found more metastases among those that consumed the thermally abused oil.

"There were twice as many tumors in the lung, and they were more aggressive and invasive," said William G. Helferich, a professor of food science and human nutrition, who led the research.

Food chemistry professor Nicki J. Engeseth, the acting head of the department, co-wrote the paper. Graduate student Ashley W. Oyirifi and U. of I. alumnus Anthony Cam were the lead authors.

"I just assumed these nodules in the lungs were little clones - but they weren't. They'd undergone transformation to become more aggressive. The metastases in the fresh-oil group were there, but they weren't as invasive or aggressive, and the proliferation wasn't as extensive," Helferich said.

In examining both groups of mice, the scientists found that the metastatic lung tumors in those that consumed thermally abused frying oil expressed significantly more of a key protein, Ki-67, which is associated strictly with cell proliferation.

Gene expression in these animals' livers was altered as well. When the researchers conducted RNA sequencing analysis, they found 455 genes in which expression was at least two times greater - or, conversely, two times lower - than in mice that consumed the fresh oil.

The altered gene pathways were associated with oxidative stress and the metabolism of foreign substances, Oyirifi said.

When oil is repeatedly reused, triglycerides are broken apart, oxidizing free fatty acids and releasing acrolein, a toxic chemical that has carcinogenic properties.

Scientists have long known that thermally abused oil contains acrolein, and studies have linked the lipid peroxides in it with a variety of health problems, including atherosclerosis and heart disease.

As the oil degrades, polymer molecules also accumulate, raising nutritional and toxicological concerns, Engeseth said.

Countries in Europe and elsewhere regulate the amount of polar materials in frying oil, which are chemically altered triglycerides and fatty acids that are used as chemical markers of oils' decomposition. Typically, these standards permit restaurants to use oil containing up to 24-27 percent polar material.

By contrast, the thermally abused oil used in the current study contained about 15 percent polar material, while fresh oil contains 2-4 percent or less, Helferich said.

"Because there are no regulations in the U.S., it's really difficult for us to evaluate what's out there," Engeseth said. "But the important thing is, the food that's fried in these oils sucks up quite a bit of oil. Even though we're not consuming the oil directly, we're consuming oil that's brought into the food during the frying process."

Breast cancer survivors' biggest fear is recurrence, and the majority of these survivors have dormant tumor cells circulating in their blood, Helferich said.

"What wakes those cells up is anybody's guess, but I'm convinced that diet activates them and creates an environment in different tissues that's more fertile for them to grow," he said.

"Many cancer biologists are trying to understand what's happening at metastatic sites to prime them for tumor growth," Oyirifi said. "We're trying to add to this conversation and help people understand that it might not be just some inherent biological mechanism but a lifestyle factor. If diet provides an opportunity to reduce breast cancer survivors' risk, it offers them agency over their own health."

An international team of researchers has built a new sensor network that can monitor two crucial activities, namely biodiversity, or the variety of life, in a particular habitat or ecosystem, and identification of possible illegal activities such as logging or poaching in protected areas. This wireless recording network is capable of recording an ecosystem's sounds with the same quality as devices that have been used to date, but it is significantly more energy-efficient and cost-effective. This network is composed of edge computing recorders, or devices that sample and process data at the recording location, with power savings of up to 280%. It promises to significantly streamline the monitoring process of biodiversity and addresses the urgent global need for new assessment methods necessary to maintain the world's biodiversity balance.

"In this paper, we propose a low cost solution for an audio recorder with onboard audio processing, as part of a wireless sensor network. The developed audio recorder can be used in several different use cases for which no cost effective, scalable biodiversity monitoring solution currently exists, such as to monitor pollinating insects, or to assess the condition of tropical forests by observing vocal animals," says Victor C. M. Leung, Ph.D., corresponding author and Professor at the Department of Electrical and Computer Engineering, University of British Columbia. "Our tests demonstrate that a collection of acoustic sounds recorded in 1 minute can arrive at the server only 30 seconds after the recording has finished, affording near real-time performance which could be of great value in tracking endangered species, or identifying illegal activity such as logging or poaching in protected areas," Professor Leung adds.

The study was published in IEEE/CAA Journal of Automatica Sinica in January 2019.

Critical to understanding an ecosystem's structure and function and predicting future changes is knowing what species inhabit an ecosystem, and how many of each kind there are. A balanced ecosystem has healthy biodiversity levels and is therefore strong enough to withstand stresses such as climate change and predators. Ensuring the ecosystem's equilibrium is therefore vital to its survival. One way to track biodiversity and ensure its balance is by monitoring the sounds that animals emit as they communicate within their environment. This is also called passive acoustic monitoring, and it has emerged as a powerful method for preserving an ecosystem's survival. However, the amount of data that is collected requires automated methods that are capable of sampling the sounds across time and space and relaying the data to an accessible storage location. As this requires a lot of power, it remains a technical challenge. As such, there is currently an urgent need for new assessment methods that are both energy efficient as well as cost effective.

"Traditional biodiversity survey methods involve the identification and logging of species, by experts at the recording location, based on what they see and hear at locations of interest. This implies several disadvantages like the vast amount of time and money to get constant results over a long period of time and a wide geographical distance, lack of reliability due to human error. Based on the growing recognition of the ecological significance of the acoustic environment, passive acoustic monitoring is emerging as a promising solution to the urgent, global need for new biodiversity assessment methods," Professor Leung adds.

In the future, the researchers aim to optimize the system's versatility as well as efficiency. They also plan to increase battery life by implementing a system sleep mode as well as integrating solar as a second power source for a long-lasting operation. Furthermore, their aims are to improve the audio quality, further reduce costs, increase the number of nodes and install antennas between them so that they can cover a larger network. "A detailed analysis to identify the balance between range and power consumption might be an interesting topic for future enhancements of the wireless recorders," Professor Leung comments.